The Role of CBP in Estrogen Receptor Cross-Talk with Nuclear Factor-κB in HepG2 Cells

Functional interactions or cross-talk between ligand-activated nuclear receptors and the proinflammatory transcription factor nuclear factor-κB (NF-κB) may play a major role in ligand-mediated modification of diseases processes. In particular, the cardioprotective effects of estrogen replacement therapy are thought to be due in part to the ability of ligand-bound estrogen receptor (ER) to inhibit NF-κB function. In the current study 17β-estradiol-bound ERα interfered with cytokine-induced activation of a NF-κB reporter in HepG2 cells. The estrogen metabolite, 17α-ethinyl estradiol, and the phytoestrogen, genistein, were also effective inhibitors of NF-κB activation, whereas tamoxifen, 4-hydroxytamoxifen, and raloxifene were inactive. This inhibition was reciprocal, as NF-κB interfered with the trans-activation properties of ERα. Ligand-bound ERα did not inhibit NF-κB binding to DNA, but it did decrease the histone acetyltransferase activity required for NF-κB transcriptional activity. Coexpression of the ...